Cellular and Chemical Biology Department, Institut Curie, PSL Research University, U1143 INSERM, UMR3666 CNRS, 26 rue d'Ulm, 75248 Paris CEDEX 05, France.
Toxins (Basel). 2017 Oct 25;9(11):340. doi: 10.3390/toxins9110340.
The cellular entry of the bacterial Shiga toxin and the related verotoxins has been scrutinized in quite some detail. This is due to their importance as a threat to human health. At the same time, the study of Shiga toxin has allowed the discovery of novel molecular mechanisms that also apply to the intracellular trafficking of endogenous proteins at the plasma membrane and in the endosomal system. In this review, the individual steps that lead to Shiga toxin uptake into cells will first be presented from a purely mechanistic perspective. Membrane-biological concepts will be highlighted that are often still poorly explored, such as fluctuation force-driven clustering, clathrin-independent membrane curvature generation, friction-driven scission, and retrograde sorting on early endosomes. It will then be explored whether and how these also apply to other pathogens, pathogenic factors, and cellular proteins. The molecular nature of Shiga toxin as a carbohydrate-binding protein and that of its cellular receptor as a glycosylated raft lipid will be an underlying theme in this discussion. It will thereby be illustrated how the study of Shiga toxin has led to the proposal of the GlycoLipid-Lectin (GL-Lect) hypothesis on the generation of endocytic pits in processes of clathrin-independent endocytosis.
细菌志贺毒素和相关肠毒素的细胞进入已被相当详细地研究。这是因为它们对人类健康构成威胁。同时，志贺毒素的研究还发现了新的分子机制，这些机制也适用于质膜和内体系统中内源性蛋白质的细胞内运输。在这篇综述中，首先将从纯机械的角度呈现导致志贺毒素进入细胞的各个步骤。将突出强调那些经常研究不足的膜生物学概念，例如波动力驱动的聚类、网格蛋白独立的膜曲率生成、摩擦力驱动的断裂和早期内体上的逆行分选。然后将探讨这些概念是否以及如何适用于其他病原体、致病因子和细胞蛋白。志贺毒素作为碳水化合物结合蛋白的分子性质及其细胞受体作为糖基化筏脂质的性质将是本次讨论的一个基本主题。通过这种方式，将说明研究志贺毒素如何导致提出 GlycoLipid-Lectin (GL-Lect) 假说，即网格蛋白独立内吞作用过程中内吞小窝的产生。
